Hepatitis C virus (HCV), the major etiologic agent of transfusion acquired non-A, non-B hepatitis. is responsible for approximately 150,000 new cases of acute viral hepatitis annually in the United States (Greenberger, N.J., 1983, "New Approaches for Hepatitis C", Contemporary Internal Medicine Feb:64). Approximately half of these infections progress to a chronic infection that can be associated with cirrhosis and/or hepatocellular carcinoma.
HCV is an enveloped, positive stranded RNA virus which has recently been classified as a separate genus within the Flavivirus family (Heinz, F. X., 1992 "Comparative Molecular Biology of Flaviviruses and Hepatitis C Virus", Arch. Virol. (Suppl.) 4:163). The viral genome is approximately 9,500 nucleotides in length and contains one long open reading frame that encodes a precursor polyprotein of 330 Kd. Individual HCV polypeptides are produced by proteolytic processing of the precursor polypeptide. This proteolysis is catalyzed by a combination of both cellular and viral encoded proteases.
In addition to the translated region, the HCV genome also contains both a 5' untranslated region (5' UTR) and a 3' untranslated region (3' UTR). The 5' UTR represents the most highly conserved sequence among all HCV isolates reported to date, and thus has been postulated to contain important regulatory elements for replication and/or translation of HCV RNAs. The 5' UTR also contains several small open reading frames (orf) but there is presently no evidence to suggest that these orf sequences are actually translated.
Development of a vaccine strategy for HCV is complicated not only by the significant heterogeneity among HCV isolates, but also by the mixture of heterogeneous genomes within an isolate (Martell, M. et al., 1992 "Hepatitis C Virus (HCV) Circulates as a Population of Different But Closely Related Genomes: Quasispecies Nature of HCV Genome Distribution", J. Virol. 66:3225). In addition, the virus contains a highly variable envelope region.
Vaccination and immunization generally refer to the introduction of a non-virulent agent against which an individual's immune system can initiate an immune response which will then be available to defend against challenge by a pathogen. The immune system identifies invading "foreign" compositions and agents primarily by identifying proteins and other large molecules which are not normally present in the individual. The foreign protein represents a target against which the immune response is made.
PCT Patent Application PCT/US90/01348 discloses sequence information of clones of the HCV genome, amino acid sequences of HCV viral proteins and methods of making and using such compositions including anti-HCV vaccines comprising HCV proteins and peptides derived therefrom.
U.S. Ser. No. 08/008,342 filed Jan. 26, 1993, U.S. Ser. No. 08/029,336 filed Mar. 11, 1993, U.S. Ser. No. 08/125,012 filed Sep. 21, 1993, PCT Patent Application Serial Number PCT/US94/00899 filed Jan. 26, 1994, and U.S. Ser. No. 08/221,579 filed Apr. 1, 1994 each contains descriptions of genetic immunization protocols. Vaccines against HCV are disclosed in each.
There remains a need for vaccines useful to protect individuals against hepatitis C virus infection. There remains a need for methods of protecting individuals against hepatitis C virus infection.